A compound already sitting on the shelves of biomedical laboratories and emergency room supply closets seems to interrupt the formation of neurodegenerative protein clumps found in Huntington’s disease, according to a preliminary animal study published August 7 in the Journal of Neuroscience.

This versatile agent, called methylene blue, gets a mention in medical literature as early as 1897 and was used to treat, at one time or another, ailments ranging from malaria to cyanide poisoning. The U.S. Food and Drug Administration has never formally approved it as a therapy for any illnesses. But that fact hasn’t stopped biomedical researchers from tinkering with the agent’s apparent ability to improve cognitive function. And although the new paper out today relies on a Huntington’s disease model in flies and mice, scientists are hopeful. "Because of existing knowledge of methylene blue and the fact that it’s not harmful to humans, I would hope that progress toward clinical trials could go relatively quickly," says Leslie Thompson, a neurobiologist at University of California–Irvine and lead author on the new study.

Huntington’s disease occurs when the C-A-G sequence of DNA base pairs repeat too often on the HTT gene, resulting in an abnormally long version of the huntingtin protein, that therefore folds incorrectly and forms clumps in the brain. The illness usually begins to affect people in their 30s and 40s, causing movement problems and early death. No drug is currently available to stop the disease from progressing.

For their experiment, researchers fed methylene blue mixed with food for a week to Drosophila flies engineered to carry a mutated copy of the HTT gene. An examination of the flies’ brains showed that protein clumps had been reduced by 87 percent compared with a control group. Meanwhile, mice designed to carry the mutated gene were given methylene blue and underwent several tests to assess mobility. At two months of age, the treated mice showed abnormal clasping of their hind claws only 20 percent of the time in a reflex test, whereas their untreated counterparts clasped at a 60 percent rate. (Less clasping meant healthier mice.) While the number of mice used was not sufficient to provide statistically significant results and the difference in the test quickly dropped off at nine weeks of age, Thompson still views the data as hopeful, because even a delay in Huntington’s symptoms would be very helpful. Thompson quickly points out that more research is needed. "The early steps of aggregation [protein clumping] are getting altered in a test tube, in flies and in mice—and that’s significant," she says, and speculates that methylene blue may possibly prevent the mutant Htt protein from sticking to itself.

What these findings mean for the approximately 25,000 to 30,000 individuals with Huntington’s disease in the U.S. right now is that a small molecule agent like methylene blue that has been grandfathered into approved use as a diagnostic tool in humans can be studied further as possible treatment for the neurodegenerative illness. "This study shows promise pre-clinically and follow-up studies are needed in a more representative mouse model that expresses the full-length Huntingtin protein and allows more study of the disease’s neurogenerative properties," says Albert La Spada, a neurogeneticist at the University of California–San Diego. Thompson underscores this point as well: "Methylene blue would absolutely require further testing in mouse models and would need safety and efficacy trial before it could be used for humans."

This article is reproduced with permission from the magazine Nature Medicine. The article was first published on April 7, 2012.